Renal Excretory System Research Articles

Three-dimensional quantitative analysis of arterial bed and elements of pelvicalyceal system of kidneys in men

The aim of the study was to investigate the patterns of three-dimensional quantitative organization of the renal artery branches in relation to the elements of the renal pelvicalyceal system in men. The study was conducted on 58 corrosion preparations of arterial vessels and renal pelvicalyceal structures obtained from men with postmortem age intervals from 22 to 75 years. As a result of the morphological study, a spatial and quantitative characteristic was given to different variants of renal artery branching, with an emphasis on their transformation into secondary vascular branches classified as zonal arteries. Additionally, a detailed analysis of the topographic and anatomical relationship between the intraorgan arterial branches of the renal artery and the excretory segments of the kidney was carried out, which made it possible to clarify the features of their spatial organization. Knowledge of the spatial arrangement of the arterial branches of the kidney, which directly correlates with the variable features of its renal pelvicalyceal apparatus and excretory system segments, opens the way to predicting potential obstacles during surgical procedures, especially during nephrolithotomy.

Abstract 284: Renal Contrast Excretion After Myelography: A Valuable Tool in The Diagnosis of Cerebrospinal‐Venous Fistulae

Introduction Cerebrospinal‐venous fistulae (CSF‐VFs) represent a pathologic, low‐flow direct connection between the intrathecal space, usually at the level of a diverticular dilation of a nerve root sleeve, and the thoracolumbar venous system. They can cause CSF hypovolemia resulting in an often‐debilitating intracranial hypotension syndrome. Lateral decubitus CT or DSA myelography (CTM, DSM) are the gold‐standard modalities for diagnosing these entities. Their high spatial and temporal resolution allows visualization of the abnormal connection between the two spaces. Yet, the small size and low flow make CSF‐VFs radiographically subtle, and may not be consistently visualized even after a correctly‐performed CTM/DSM, requiring repeated invasive procedures to definitively establish or exclude their presence. Opacification of the renal excretory system 30‐60 minutes after lateral decubitus myelograms is thought to be a highly sensitive and specific indirect sign of the presence of a CSF‐VF 1,2, as this amount of time is considered insufficient to allow arachnoid reabsorption of contrast. Renal pelvises hyperdensity or its absence after a negative decubitus CTM/DSM can prompt further myelographic investigation or definitively rule out the presence of a CSF‐VF on the side of the examination, respectively. Methods We present three patients with severely symptomatic CSF‐VFs treated at our hospital between 2021 and 2023. All patients were females (range: 50‐60 years old). All three patients underwent bilateral diagnostic lateral decubitus DSM/CTM. Exams were performed at least 72 hours apart in order to allow complete clearance of intrathecal contrast. After each myelographic acquisition, patients remained in the lateral decubitus position until abdominal CT imaging was performed at 30 and 45 minutes to detect the presence of contrast in the renal collecting system. Results Patients 1 and 2, had a CSF‐VF between nerve root dural diverticula and the azygos system that was directly visualized on lateral decubitus CTM (patient 1: right T10‐T11, patient 2: left T8‐T9). Contrast was detectable in the renal pelvises after myelography was performed on the affected side, and not detectable after the contralateral investigation. One fistula was treated via CT‐guided targeted blood patch and fibrin glue injection and the other via endovascular Onyx embolization of the tributary Intercostal veins. Patient 3 had an extremely slow flow CSF‐VF at the right T11‐12 level that was identified only after 5 right‐sided decubitus myelograms with both modalities. The repeated exams were based on the presence of contrast in the renal pelvises after each right‐sided procedure and on the absence of renal opacification after the left‐sided myelograms. Eventually, a CSF‐VF was identified. Successful Onyx embolization of the foraminal veins of the R T11‐12 levels was performed. All three patients had complete resolution of symptoms. Conclusion Contrast presence in the renal excretory system after a lateral decubitus CTM/DSM is a potentially highly sensitive and specific indirect diagnostic sign that can establish or exclude the presence of a CSF‐VF on the examined side. It could be particularly helpful when the fistula is not initially detected, as it can prompt aggressive continuation of the myelographic work‐up. Similarly, it can exclude its presence on one side, sparing the patient invasive and low yield diagnostic procedures.

Accurate detection and delineation boundary of renal cell carcinoma based on dual-targeted magnetic-fluorescent carbon dots

Accurate tumor localization and tumor boundary delineation are significant to improve the effectiveness of cancer therapeutics. In the present study, a fluorescence/magnetic resonance (MR) nanoprobe AS1411-CLT1-Gd-CDs with dual targeting function was developed for precise detection and delineation boundary of renal cell carcinoma (RCC). The dual-targeted AS1411-CLT1-Gd-CDs nanoprobe was initially established by co-conjugating peptide CLT1 and aptamer AS1411 to magnetic-fluorescent gadolinium(III)-doped carbon dots (Gd-CDs). The proposed AS1411-CLT1-Gd-CDs with wide-range multi-color fluorescence emission could target-specific image 786-O RCC cells through three distinct fluorescence channels and achieved the quantitativedetermination of 786-O cells with a low detection limit of 552 cells mL−1. Besides, the dual-targeted AS1411-CLT1-Gd-CDs nanoprobe could accurately delineate tumor boundary and generate greater and prolonged plateau contrast enhancement than the non-targeted and single-targeted Gd-CDs. Furthermore, the small-sized nanoprobe could be easily excreted from the body by the renal excretory system after imaging without any obvious long-term toxicity. These studies demonstrated that the proposed dual-targeted nanoprobe appeared as a very promising fluorescence/MR imaging agent for accurate identification and localization of renal cancer tumors, which could be beneficial to the early diagnosis and treatment of RCC.

Opuntia ficus-indica the key plant in climate change: characteristics, cultivation and uses

The Opuntia genus, belonging to the Cactaceae family, has about 300 species, of which Opuntia ficus indica, or Prickly Pear, is considered the best known and most significant. Opuntia ficus indica have been used in Mexico and Latin America since pre-hispanic times as a food and medicinal resource. In recent years, prickly pear cultivation has increased mainly because this plant used for food, medicinal and livestock purposes is able to withstand extreme drought conditions in relatively poor soils. The fruits of the prickly pear are of various colours such as yellow, orange, purple and white, and when ripe their sweet pulp is characterised by a low acidity. It possesses numerous nutritional and therapeutic virtues such as richness in carbohydrates, vitamins, minerals and considerable antioxidant, anti-diabetes, anti-cancer fruit activity. Opuntia also has laxative properties due to its soluble fibres and mucilage. The infusion of the harvested and dried flowers has a depurative effect; it has a mild, gentle diuretic and relaxing action on the renal excretory system. Opuntias are also exploited as an alternative and cheap source of source of food for animals and as an ornamental plant. Opuntia ficus indica is grown in subtropical, tropical and warm-temperature areas; it is mainly cultivated in Tunisia, Libya and Egypt. The Prickly Pear finds a particularly favourable habitat in Sardinia, Calabria, Apulia and Sicily, where it is also cultivated, as well as in Spain and North Africa, for the exploitation of its edible fruit, with its delicately sweet pulp, rich in minerals, especially calcium and phosphorus, and vitamin C. In this review, the characteristics, cultivation methods, main uses of the plant and fruits, market and adversities of Opuntia ficus indica are described.

Gas-containing renal stones: a red flag for renal infection.

Gas in the renal excretory system is described as a consequence of recent procedures but it can be a sign of severe conditions such as fistulas or infections; however, gas-containing renal stones are only rarely encountered. To describe the association of gas-containing renal stones and urinary tract infection. We performed a retrospective evaluation of the clinical and imaging findings in a series of six patients with gas-containing renal stones and compared our findings with those of patients with gas-containing renal stones reported in the literature. Urine and stone cultures were used as a diagnostic standard for urinary tract infection. Including the present series, there is a total of 21 patients with gas-containing renal stones in the literature. Based on clinical presentation, urinary tract infection could be suspected in 10 (57%) patients, while urine and/or stone cultures showed infection in 18 of 19 (95%) patients, with only one case with no bacterial growth in both (5%); in the remaining patient the information was not available. Gas-containing renal stones are a rarely reported entity usually diagnosed with computed tomography. They are a radiological sign often associated with urinary tract infection that can also be encountered in patients with non-specific renal symptoms.

Complete Bilateral Ureteral Duplication: A Case Study on Anatomic Variations

Developmental variation is frequently observed during anatomical study. Some variations remain asymptomatic and do not interfere with normal function but others may have significant clinical consequences. Developmental anomalies of the renal excretory system are not uncommon. Knowledge of the variation in ureteral development is essential in determining the management strategies of urogenital disorders. Partial or complete duplication of the ureter may result from early splitting of the ureteric bud or the presence of a second ureteric bud. Here we report a case of congenital anomaly in the ureterorenal system where complete bilateral ureteral duplication was found in a female cadaver donor. Both sets of ureters entered the urinary bladder enclosed in a common fascial sheath but opened separately into the trigone of the bladder. In this case, no evident renal pathology was observed. There was no sign of renal cysts, hydronephrosis or calculus in either kidney. This case highlights the importance of learning morphological variations to students of health science.

Morpho- Functional Observations on Ontogenic development of the Renal excretory system in pre to post flexion stages larvae of Himalaya Snow trout Schizothorax plagiostomus (Heckel)

Schizothorax plagiostomus is one of the most important food fish inhabiting the snow-fed tributaries of the Himalayan region. Due to nutritional value, good growth rate, high economic prospects as well as the decline in the natural habitat its commercial production is desired. Keeping in view this fact, during the present investigation by following the artificial breeding and rearing experiments an attempt has been made to understand the morpho-functional development of the renal excretory system in pre to post-flexion stages larvae. The study reveals that all the essential basic structures of the renal excretory system (pronephros) were established before the initiation of external feeding. During the post-flexion stage when the yolk sac was almost reabsorbed and larvae exclusively depend on exogenous feeding the mesonephric tubules were forming and some of them become functional i.e. presence of glomerulus to maintain the internal environment as well as efficient removal of gradually increasing amount of nitrogenous wastes. The presence of lymphoid tissues was suggesting that cell-mediated immune responses develop progressively in the Himalayan snow trout S. plagiostomus larvae.

Renal Excretion of Contrast on CT Myelography: A Specific Marker of CSF Leak

The purpose of this study was to evaluate the sensitivity and specificity of renal/ureteric opacification on postmyelographic CT as a sign of CSF leak. We performed a retrospective review of postmyelographic CT scans from 49 consecutive patients seen between January 2008 and August 2018 with imaging and/or clinical findings related to intracranial hypotension. Each scan was evaluated by both a neuroradiology fellow and a board-certified neuroradiologist for the presence of contrast in the renal excretory system. A similar assessment was also performed on 90 consecutive control subjects who underwent CT myelography for alternative indications. Among the 49 patients with suspected CSF leak, 21 (43%) had an overt CSF leak on postmyelographic CT (group 1) and 28 (57%) did not (group 2). Overall, renal contrast was identified in 7/49 patients (14.3%): 5 (24%) patients in group 1, and 2 (7%) patients in group 2. Renal contrast was not seen in any of the 90 controls on postmyelographic CT. Renal contrast was exclusively seen in patients with a clinically or radiographically suspected CSF leak. Given its 100% specificity, identification of this finding should prompt a second look for subtle myelographic contrast extravasation or an underlying CSF-venous fistula. Our results suggest that this sign may be considered an additional diagnostic criterion for CSF leak in the absence of an identifiable leak.

Emphysematous Pyelonephritis: Case Series and Review of the Literature

Introduction: Emphysematous pyelonephritis (EPN) is a rare gas-forming infection of renal parenchyma and excretory system and surrounding renal areas. It has a low incidence but high mortality (15-20%). Objectives: Our goal is to report our series of EPN and review the literature about this entity to improve its management. Materials and Methods: We analyze three EPN cases, in our Centre from 2017 to 2019, two women and one man between 45-84-years-old. Common symptoms were pain and fever with fatal evolution to septic shock in one of them. Medical management was adopted in all of them. Percutaneous nephrostomy was needed in two cases to complete treatment. And one case of dry type EPN required an urgent nephrectomy. Escherichia coli was isolated in all cases. Mortality rate reached 33.3%. Discussion and Conclusion: EPN is a rare and severe necrotizing infection of renal parenchyma and its surrounding areas. It appears most commonly in females (6: 1). Diabetes mellitus is the main risk factor and urinary obstruction occurs in 25- 40%. Escherichia coli is isolated in 70%. There are many classifications to establish the best treatment according to stage. The most complete is Huang and Tseng classification (2000), based on CT radiological findings. Systolic pressure <90 mmHg, thrombocytopenia, bilateral EPN are associated with poor prognosis. Early medical treatment is essential. The most accepted management consist of support measures with percutaneous nephrostomy. In not-responding patients and those with bad prognosis, urgent nephrectomy can be necessary.

Is emphysematous pyelitis a precursor lesion of emphysematous pyelonephritis? A case report of bilateral emphysematous pyelitis caused by extended-spectrum beta-lactamase Escherichia coli and literature review

The presence of air in different parts of renal excretory system needs accurate assessment, and careful consideration as its progression to renal parenchyma can lead to fulminant course with substantial mortality. Bilateral emphysematous pyelonephritis is a well-known entity, but bilateral emphysematous pyelitis (EP) along with emphysematous cystitis is extremely rare. An internet search with the term “bilateral emphysematous pyelitis” and “bilateral emphysematous pyelitis and ureteritis with cystitis” only found three case reports in English. We present an interesting case of bilateral EP, ureteritis, and cystitis in a nondiabetic male patient without any history of immunodeficiency (HIV or chronic steroid use) but with a history of nonobstructing bilateral multiple renal calculi who was successfully managed medically. EP, if diagnosed early and managed properly, has an excellent prognosis with complete recovery following medical treatment. The following core competencies are addressed in this article: Practice-Based Learning and Improvement, Patient care and Procedural skills, Medical Knowledge.

The diapause program impacts renal excretion and molecular expression of aquaporins in the northern house mosquito, Culex pipiens

Adult females of the mosquito Culex pipiens entering diapause increase sugar water ingestion and reduce evaporative water loss, but how these attributes of the diapause program impact activity of the renal excretory system remains unknown. Here we compared the renal excretory capacity of diapausing and non-diapausing females, as well as the molecular expression of aquaporin (AQP) genes that encode channels involved in transporting water and/or small metabolites. Baseline urine excretion rates in diapausing mosquitoes were higher than in those of their non-diapausing counterparts, possibly a consequence of the intense sugar feeding associated with diapause. But, diapausing mosquitoes exhibited a much lower capacity for diuresis than non-diapausing mosquitoes. The suppressed diuretic capacity likely reflects reduced investment in the energetically-expensive post-prandial diuresis, an event not observed in diapausing mosquitoes. The mRNA expression levels of two genes encoding AQPs, Eglp1 and Aqp12L, in diapausing mosquitoes were down-regulated (on day 14) and up-regulated (on both days 3 and 14), respectively, in whole body samples. These changes were not evident in the excretory system (i.e., Malpighian tubules and hindgut), which showed no differential expression of AQPs as a function of diapause. Several AQP mRNAs were, however, differentially expressed in the midgut, ovaries, and abdominal body wall of diapausing mosquitoes, suggesting that AQPs in these tissues may be playing important non-excretory roles that are unique to diapause physiology.

Effects of High Altitude Exposure on Physiology and Pharmacokinetics.

High-altitude environments are known to result in a broad range of physiological changes in human body, which may influence various pharmacological processes and pharmacokinetics. A series of physiological systems reacting to a high-altitude stressor and the effects of these physiological alterations on pharmacokinetics have been investigated for decades. In this review, we summarized the effects of high altitude on human physiological alterations (including those in the gastrointestinal system, cardiovascular system, pulmonary system, hematocrit, drug metabolism enzyme system, and renal excretory system), as well as subsequent changes of pharmacokinetics (such as absorption, distribution, metabolism, and excretion of drugs). In summary, it isclear that high altitudes can lead to a broad range of physiological changes, leading to the changes in the ADME process of drugs. According to previous pharmacokinetics studies in human, the pharmacokinetics changes due to high altitude exposure may require dosage regimen modifications to maintain drug efficacy and safety, which should draw our attention to drug administration dosage for those planning ascent to high altitudes.

Clinical imaging contrast agents - inception through lifecycle

Event Abstract Back to Event Clinical imaging contrast agents - inception through lifecycle Benjamin Yeh1 1 University of California, San Francisco, Radiology and Biomedical Imaging, United States Introduction The introduction of injectable contrast agents transformed medical imaging such that CT and MRI became critical first line tests for broad spectrums of clinical diagnosis and treatment monitoring. Importantly, it was the interplay between medical scanner breakthroughs and contrast agent availability that was central driving up the value of diagnostic imaging in the past half century. As medical imaging scanners improved, our understanding of how contrast agents can be tailored to optimally highlight disease became amongst the most critical topics of medical research. Discussion The usage of existing clinical contrast agents is now radically different than what was initially conceived when the agents were first introduced. For example, iodinated contrast agents were initially introduced for the sole purpose of highlighting the renal excretory system at plain film imaging. Since then, iodinated agents have taken on vastly increased roles for defining vasculature at minimally invasive angiographic studies and for defining global anatomy in CT scans. Further introduction of variant iodinated benzene rings with different physicochemical properties opened new imaging applications, such as cholangiographic and safer intravenous imaging. Similarly, the introduction of new imaging technology such as helical multislice CT and dual energy imaging dramatically changed the capabilities of the entire class of iodinated agents. Similar changes occurred with gadolinium-based MRI contrast material which quickly altered the landscape of MR imaging across all organ systems. However, as usage proliferated, so did the understanding of toxicities from contrast agents. Some toxicities, such as preventative measures for contrast-induced nephropathy and metformin-related lactic acidosis, became deeply ingrained in clinical practice even though the prevalence and severity of such entities were not well studied and subsequently were found to be far lower than initially thought. Conversely, toxicities of gadolinium chelates were exposed only after decades of use and resulted in near crisis as the magnitude of the contrast-related disease was studied. Conclusion: The understanding of the intimate connection between medical scanner capabilities and inevitable evolution and biomedical contrast material physicochemical properties is critical to consider for the development of any new contrast agent. Keywords: MRI, contrast agent, biomedical application Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Imaging with biomaterials Citation: Yeh B (2016). Clinical imaging contrast agents - inception through lifecycle. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02933 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Benjamin Yeh Google Benjamin Yeh Google Scholar Benjamin Yeh PubMed Benjamin Yeh Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Analysis of the effect of renal excretory system cooling during thermal radiofrequency ablation in an animal model

Analysis of renal excretory system integrity and efficacy of radiofrequency ablation with and without irrigation with saline at 2°C (SF2). The median third of sixteen kidneys were submitted to radiofrequency (exposition of 1 cm) controlled by intra-surgical ultrasound, with eight minutes cycles and median temperature of 90°C in eight female pigs. One excretory renal system was cooled with SF2, at a 30mL/min rate, and the other kidney was not. After 14 days of post-operatory, the biggest diameters of the lesions and the radiological aspects of the excretory system were compared by bilateral ascending pyelogram and the animals were sacrificed in order to perform histological analysis. There were no significant differences between the diameters of the kidney lesions whether or not exposed to cooling of the excretory system. Median diameter of the cooled kidneys and not cooled kidneys were respectively (in mm): anteroposterior: 11.46 vs. 12.5 (p = 0.23); longitudinal: 17.94 vs. 18.84 (p = 0.62); depth: 11.38 vs. 12.25 (p = 0.47). There was no lesion of the excretory system or signs of leakage of contrast media or hydronephrosis at ascending pyelogram. Cooling of excretory system during radiofrequency ablation does not sig¬nificantly alter generated coagulation necrosis or affect the integrity of the excretory system in the studied model.

Probenecid inhibition of the renal excretion of dyphylline in chicken, rat and man.

The effect of probenecid on the renal excretion of dyphylline was studied in chicken, rat and man. Dyphylline was found to be actively excreted when measured by the Sperber preparation in hens, the isolated perfused kidney of the rat and clearance studies in man. In each study probenecid significantly decreased dyphylline excretion demonstrating that dyphylline occupied the renal organic anion transport system. This same drug interaction, at the level of the renal excretory system, in these three species occurred at comparable concentrations of dyphylline and probenecid.

Production of [F-18]fluoroannexin for imaging apoptosis with PET.

Recombinant human-annexin-V was conjugated with 4-[F-18]fluorobenzoic acid (FBA) via its reaction with the N-hydroxysuccinimidyl ester (FBA-OSu) at pH 8.5. A series of reactions using varying amounts of annexin-V, unlabeled FBA-OSu, and time produced products with different conjugation levels. Products were characterized by mass spectrometry and a cell-binding assay to assess the effect of conjugation. In each case, the conjugated protein was a mixture of proteins with a range of conjugation. Annexin-V could be conjugated with an average of two FBA mole equivalents without decreasing its affinity for red blood cells (K(d) 6-10 nM) with exposed phosphatidylserine. An average conjugation of 7.7 (range 3-13) diminished the binding 3-fold. Large-scale production and purification of [F-18]FBA-OSu from [F-18]fluoride was accomplished within 90 min and in 77% radiochemical yield (decay-corrected to the end of cyclotron bombardment). The conjugation reaction of annexin with [F-18]FBA-OSu was studied with respect to activity level, protein mass, and concentration. Under the most favorable conditions, >25 mCi [F-18]fluoroannexin (FAN) was isolated in 64% yield (decay-corrected for a 22 min conjugation process) from labeling 1.1 mg of annexin-V. A pilot PET imaging study of [F-18]fluoroannexin in normal rats showed high uptake in the renal excretory system and demonstrated sufficient clearance from most other internal organs within 1 h. [F-18]Fluoroannexin should prove useful in imaging targeted apoptosis.

Subchronic Oral Toxicity Studies with Erythritol in Mice and Rats

Erythritol is a sugar alcohol (polyol) with potential applications as a low-calorie, bulk sweetener. Ingested erythritol is efficiently absorbed and excreted unchanged via the urine since it is not metabolized systemically by the animal or human body. Erythritol was administered to four groups of 10 male and 10 female Swiss CD-1 mice and four groups of 15 male Wistar Crl:(WI) WU BR rats at dietary levels of 0, 5, 10, or 20% for 90 days. A fifth group of rats received a diet containing 20% erythritol on a time-restricted basis (6 hr/day), and a sixth group received a diet containing 20% mannitol for comparison. There were no treatment-related mortalities in either mice or rats. Soft stools and occasional diarrhea were observed in rats fed diets with 20% erythritol or mannitol but not in mice. Body weights were slightly yet significantly reduced in rats fed 20% erythritol or mannitol and in male mice of the 20% dose group. Erythritol intake in the high-dose group was approximately 12 g/kg body wt in rats and 44 and 45 g/kg body wt in male and female mice, respectively. Hematological and clinicochemical examinations of blood and plasma did not reveal any treatment-related effects. Urine output increased with increasing erythritol dose. In male and female mice of the 20% erythritol group, the creatinine-normalized urinary excretion of protein, K-glutamyltransferase (GGT), and electrolytes (Na+, K+, Ca2+, Pi, citrate) was significantly increased while urinaryN-acetylglucosaminidase (NAG) remained unchanged. At the 10% level, significantly increased urinary protein (both sexes) and GGT (males only) excretion were seen. In rats, the creatinine-normalized urinary excretion of GGT, NAG, and some electrolytes (Na+, K+, and Ca2+) was increased in some erythritol groups but a clear dose–response relationship was evident only for calcium. On termination of the study, cecal enlargement was seen in rats of the 10 and 20% dose groups and in mice of the 20% dose group. Increased relative and absolute kidney weights were observed in both sexes of mice in the 20% erythritol group, in male mice of the 5 and 10% groups, and in rats of the 10 and 20% erythritol groups. Histopathological examination did not reveal any treatment-related abnormalities in either mice or rats. In conclusion, the ingestion of erythritol for 90 days at dietary levels of up to 20% did not produce signs of toxicity in mice or rats. In particular, the morphological integrity of the kidneys was not adversely affected by the treatment in either species. The increases in urinary excretion of protein, GGT, NAG, and electrolytes were considered to result from extensive osmotic diuresis and a potential overload of the renal excretory system at the high dose levels employed.

Evidence for the Involvement of an Anion Exchanger in Cortisol Release from Bovine Adrenocortical Cells

In this study the influence of probenecid as inhibitor of the renal excretory system for organic anions was tested on the release of cortisol from primary cultures of bovine adrenocortical cells. ACTH-stimulated cortisol release (30 min to 24 h) was inhibited by probenecid (Ki = 0.093 mM). Analysis of steroid synthesis with ³H-pregnenolone as precursor indicated that part of the inhibition resulted from an attenuation of steroid synthesis by probenecid. The increased intracellular cortisol levels in the presence of probenecid however indicate an inhibitory effect on an efflux mechanism. Cortisol efflux was trans-stimulated by <i>p</i>-aminohippurate (PAH) and tetrafluorosuccinate, substrates of the renal PAH/anion exchanger. Further evidence for the PAH exchanger provided the expression of a probenecid-sensitive PAH transporter after injection of mRNA from adrenal cells into <i>Xenopus laevis </i>oocytes.

Organic cation secretion by Cancer borealis urinary bladder.

In the crab, Cancer borealis, initial clearance studies showed a potent renal excretory system for the model organic cation, tetraethylammonium (TEA). TEA clearance averaged 145 +/- 32 ml/day, which was 18 times the paired polyethylene glycol clearance. TEA uptake by slices of urinary bladder was concentrative, saturable, inhibitable by N1-methylnicotinamide chloride, and dependent on glycolytic, but not oxidative, metabolism. When mounted in flux chambers, bladders exhibited a large net secretory flux. For 0.1 mM TEA, the ratio of secretory to reabsorptive fluxes was 65. Urinary bladders from another crab, Cancer irroratus, and a lobster, Homarus americanus, also exhibited net TEA secretion. In C. borealis bladder, secretory transport was concentrative, saturable, and nearly abolished by addition of 1 mM quinine to the serosal bath. Reabsorptive transport was not concentrative and was not reduced by luminal quinine. The data are consistent with a secretory pathway that is transcellular and mediated by carriers at both the serosal and luminal membranes.

Studies on the mechanism for renal elimination of N-acetylphenylalanine: its pathophysiologic significance in phenylketonuria.

To elucidate the mechanism and biologic significance of urinary occurrence of N-acetylphenylalanine in phenylketonuria, the metabolic fate of N-acetylphenylalanine was studied in rats. In vivo and in vitro analysis revealed that N-acetyl-14C(ul)-phenylalanine bound to plasma albumin with an association constant of 8.52 X 10(3) M-1 and that the number of binding sites was 0.98 per mole albumin. Intravenously administered N-acetylphenylalanine was rapidly extracted from the circulation predominantly by the kidney and excreted into urine. Plasma clearance of the injected ligand was markedly decreased by bilateral nephrectomy but not by bilateral ureter ligation. Probenecid, a potent inhibitor of the renal excretory system for organic anions, such as hippuric acid, sharply decreased the rate of disappearance from the circulation, renal accumulation, and urinary secretion of intravenously administered N-acetylphenylalanine. These results indicate that intravenously administered N-acetylphenylalanine undergoes renal peritubular transport via a probenecid-sensitive excretory system for organic anions. This renal transtubular excretory mechanism may possibly operate in elimination of N-acetylphenylalanine, a hazardous amphipathic metabolite of phenylalanine, from plasma into urine in phenylketonuric patients.